Abstract for IMM94001

Immunotoxicity of Carbon Tetrachloride in Female B6C3F1 Mice

Abstract

The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the U.S. Government.

Carbon tetrachloride was nominated to the NTP for toxicological evaluation and was selected for immunotoxicity studies by the chemical manager. Thus, the purpose of these range-finding studies was to determine the doses of carbon tetrachloride to be used in the protocol to determine the potential effects of carbon tetrachloride on the immune system.

The range-finding studies were conducted in female B6C3F1 mice. The animals were administered carbon tetrachloride daily for 14 days by oral gavage. Carbon tetrachloride was prepared as a solution in corn oil. In completing the range-finding protocol, three studies were conducted. In the first and second studies, three dose levels of carbon tetrachloride were used. The doses administered were 100, 500, and 1000 mg/kg. In the third study, doses of 25, 50, 100, and 500 mg/kg were used.

The results of the carbon tetrachloride range-finding studies demonstrate that, in the female B6C3F1 mouse, exposure to carbon tetrachloride, administered by oral gavage for 14 days at doses of 1000 mg/kg or less, was not overly toxic in that all of the animals survived the exposure period. In general, there were no effects on body weight or body weight gain following carbon tetrachloride exposure. As expected, exposure to carbon tetrachloride produced a significant increase in liver weight and an elevation in serum glutamic pyruvic transaminase. A consistent decrease was observed in the plaque-forming cell assay on the IgM response to the T-dependent antigen sheep erythrocytes at doses of 500 mg/kg and greater, and a decrease in the mixed leukocyte response was also observed at the 500 mg/kg and above dose levels.

Based on the toxicological and immunological results of these range-finding studies, doses of 50, 100, and 500 mg/kg will be used in the carbon tetrachloride 14-day protocol study.